{"id":13422,"date":"2023-12-29T15:37:00","date_gmt":"2023-12-29T15:37:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&p=13422"},"modified":"2026-01-29T15:59:47","modified_gmt":"2026-01-29T15:59:47","slug":"discovery-of-five-sos2-fragment-hits-with-binding-modes-determined-by-sos2-x-ray-cocrystallography","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/discovery-of-five-sos2-fragment-hits-with-binding-modes-determined-by-sos2-x-ray-cocrystallography\/","title":{"rendered":"Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography"},"content":{"rendered":"\n

Christopher R. Smith, Dan Chen,James G. Christensen, Ren\u00e9 Coulombe<\/strong>, James F\u00e9thi\u00e8re<\/strong>, Robin J. Gunn, Johan Hollander, Benjamin Jones, John M. Ketcham, Shilpi Khare, Jon Kuehler, J. David Lawson, Matthew A. Marx, Peter Olson, Kelly E. Pearson, Cynthia Ren, Denise Tsagris, Thirumalaiselvi Ulaganathan<\/strong>, Inge Van\u2019t Veer, Xiaolun Wang, Anthony Ivetac<\/p>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

SOS1 and SOS2 are guanine nucleotide exchange factors that mediate RTK-stimulated RAS activation. Selective SOS1:KRAS PPI inhibitors are currently under clinical investigation, whereas there are no reports to date of SOS2:KRAS PPI inhibitors. SOS2 activity is implicated in MAPK rebound when divergent SOS1 mutant cell lines are treated with the SOS1 inhibitor BI-3406; therefore, SOS2:KRAS inhibitors are of therapeutic interest. In this report, we detail a fragment-based screening strategy to identify X-ray cocrystal structures of five diverse fragment hits bound to SOS2.<\/p>\n\n\n\n

Ref: J Med Chem 2024<\/a><\/p>\n\n\n\n

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